Melanoma-associated antigen 3-derived peptide presented by Human Leukocyte Antigen A2 (MAGEA3-HLA-A2)

The Melanoma-associated antigen 3-derived peptide presented by Human Leukocyte Antigen A2 (MAGEA3-HLA-A2) is a peptide-major histocompatibility complex (pMHC) that serves as a tumor-specific target for immunotherapy. MAGE-A3 is a cancer-testis antigen (CTA) that is highly expressed in various malignancies, such as melanoma and non-small cell lung cancer, but is absent in normal adult tissues except for the testis (UniProt). Intracellular MAGE-A3 is processed into immunogenic peptides, most notably KVAELVHFL (residues 112-120) and FLWGPRALV (residues 271-279), which are presented on the cell surface by the HLA-A2 molecule (NIH). This complex is targeted by T-cell receptor (TCR)-engineered T cells and cancer vaccines to induce a cytotoxic T-cell response against tumors (PubMed). However, clinical development has been complicated by severe safety concerns, including fatal neurotoxicity caused by the cross-recognition of MAGE-A12 in the brain (NIH). Despite these challenges, the MAGEA3-HLA-A2 complex remains a key target for developing high-precision adoptive cell therapies.

Other names

MAGE-A3/HLA-A*02:01MAGE-A3/HLA-A2 complexKVAELVHFL-HLA-A2FLWGPRALV-HLA-A2MAGE-A3 peptide-MHC complexMAGE-A3/HLA-A2 pMHC

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and tumor cell lysis.